title: A population-based study of low-grade gliomas and mutated isocitrate dehydrogenase 1 (IDH1).
abstract: Low-grade gliomas (LGG) have a slow growth rate, but transformations into malignant gliomas with a rapid deterioration occur in many patients. The aim of this study was to evaluate clinical prognostic factors in a population-based cohort of patients with LGG. In addition we investigated the expression and prognostic value of the isocitrate dehydrogenase 1 (IDH1) R132H mutation. Seventy-four patients diagnosed between 2005 and 2009 in the Region of Southern Denmark were identified using the Danish Cancer Register and The Danish Pathology Databank. Survival analysis using Cox regression was performed in 52 patients with tumor samples useable for immunohistochemical evaluation of IDH1 status. Patients with a contrast enhancing tumor, neurological deficits, headache, an astrocytic tumor and PS 2-4 had an increased risk of recurrence. In univariate analysis age > 50 years (HR 2.14, 95 % CI 1.08-4.24), having neurological deficit (HR 2.28, 95 % CI 1.15-4.52), receiving post-surgical treatment (HR 2.52, 95 % CI 1.19-5.32), being in performance status 2-4 (HR 1.44, 95 % CI 1.15-1.81), and having an astrocytic tumor (HR 3.79, 95 % CI 1.64-8.73) were associated with poor survival. Mutated IDH1 (mIDH1) was identified in 46 % of the patients and was significantly correlated to a good survival in both univariate (HR 0.24, 95 % CI 0.11-0.53) and in multivariate analysis (HR 0.40, 95 % CI 0.17-0.91). The other clinical variables were not significant when adjusted for the effect of mIDH1 status. We find that young age, the absence of neurologic deficit, PS 0-1 and oligodendroglial histology were associated with better survival. IDH1 status showed independent prognostic information when adjusting for classical prognostic factors, and should be validated in a larger patient population.
authors.affiliation: Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense, Denmark. rikke.dahlrot@ouh.regionsyddanmark.dk
authors.forename: Rikke H
authors.initials: RH
authors.lastname: Dahlrot
authors.forename: Bjarne W
authors.initials: BW
authors.lastname: Kristensen
authors.forename: Jacob
authors.initials: J
authors.lastname: Hjelmborg
authors.forename: Jørn
authors.initials: J
authors.lastname: Herrstedt
authors.forename: Steinbjørn
authors.initials: S
authors.lastname: Hansen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human